Photocycloaddition of biscyclopropyl alkenes to C60: An unprecedented approach toward cis-1 tricyclic-fused fullerenes

Article abstract of DOI:10.1021/ol201112a

A novel, simple, and entirely regioselective tandem cycloaddition of biscyclopropyl-substituted alkenes to [60]fullerene has been revealed. This reaction affords cis-1 tricyclic-fused organofullerenes bearing the hitherto elusive 5-4-5 fused tricyclic ring system.

Full text of DOI:10.1021/ol201112a

ORGANIC
LETTERS
2011
Vol. 13, No. 13
3364–3367
Photocycloaddition of Biscyclopropyl
Alkenes to C60: An Unprecedented
Approach toward cis-1 Tricyclic-Fused
Fullerenes
Manolis D. Tzirakis, Mariza N. Alberti, and Michael Orfanopoulos*
Department of Chemistry, University of Crete, GR 71003, Heraklion, Greece
orfanop@chemistry.uoc.gr
Received April 27, 2011
ABSTRACT
A novel, simple, and entirely regioselective tandem cycloaddition of biscyclopropyl-substituted alkenes to [60]fullerene has been revealed. This
reaction affords cis-1 tricyclic-fused organofullerenes bearing the hitherto elusive 5ꢀ4ꢀ5 fused tricyclic ring system.
Cyclopropane-containing compounds are important
and versatile building blocks in organic synthesis. They
have been extensively used for the synthesis of carbo-
cyclic ring systems including five- to nine-membered
carbocycles.1,2 In this context, we previously investigated
the reactivity of vinyl monocyclopropane derivatives with
different electrophiles, including C60.3 In sharp contrast,
however, to their monocyclopropane analogues, the syn-
thetic utility of biscyclopropane derivatives is still in its
infancy. To date, there are only two examples of synth-
etic applications of such systems, which include the
preparation of carbocyclic seven-membered rings4a and
N-containing heterobicycles, respectively.4b Herein we re-
port the unprecedented photochemical cycloaddition of
biscyclopropyl-substituted alkenes with C60. This simple
one-step reaction proceeded in a totally regioselective
manner affording in good yield the first example of cis-1
fullerene isomers featuring the hitherto elusive 5ꢀ4ꢀ5
tricyclic fused ring system. Semipreparative HPLC was
employed to circumvent the inherently difficult challenge
of separating and purifying all four stereoisomeric ad-
ducts, thus allowing for their unequivocal structural char-
acterization by means of spectral studies (i.e., 1D/2D
NMR, HRMS, UVꢀvis).
(1) Selected reviews: (a) Carson, C. A.; Kerr, M. A. Chem. Soc. Rev.
2009, 38, 3051. (b) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev.
2007, 107, 3117. (c) Thematic Issue on Cyclopropanes and Related
Rings. Chem. Rev. 2003, 103, 931. (d) Wong, H. N. C.; Hon, M. Y.; Tse,
C. W.; Yip, Y. C.; Tanko, J.; Hudlicky, T. Chem. Rev. 1989, 89, 165.
(2) For recent examples, see: (a) Saito, S.; Maeda, K.; Yamasaki, R.;
Kitamura, T.; Nakagawa, M.; Kato, K.; Azumaya, I.; Masu, H. Angew.
Chem., Int. Ed. 2010, 49, 1830. (b) Bhargava, G.; Trillo, B.; Araya, M.;
Our first goal was the preparation of 5- to 12-membered
fused ring systems on C60. To this purpose, we prepared
vinyl biscyclopropane derivatives9 and 10(Scheme 1);5 the
key intermediate for this synthesis was the cyclopropanation
of compound 4 with oxosulfonium salt 5.5,6a,7 The presence
of a double bond next to the biscyclopropyl moiety was a
prerequisite to observe the subsequent strain-driven cleavage
ꢀ
~
Lopez, F.; Castedo, L.; Mascarenas, J. L. Chem. Commun. 2010, 46, 270.
(c) Inagaki, F.; Sugikubo, K.; Miyashita, Y.; Mukai, C. Angew. Chem.,
Int. Ed. 2010, 49, 2206 and references therein.
(3) (a) Alberti, M. N.; Orfanopoulos, M. Org. Lett. 2009, 11, 1659. (b)
Alberti, M. N.; Orfanopoulos, M. Org. Lett. 2008, 10, 2465. (c)
Hatzimarinaki, M.; Orfanopoulos, M. Org. Lett. 2006, 8, 1775. (d)
Hatzimarinaki, M.; Roubelakis, M. M.; Orfanopoulos, M. J. Am.
Chem. Soc. 2005, 127, 14182.
(4) (a) Kim, S. Y.; Lee, S. I.; Choi, S. Y.; Chung, Y. K. Angew. Chem.,
Int. Ed. 2008, 47, 4914. (b) Kim, S. Y.; Kang, Y. K.; Chung, Y. K.
Chem.;Eur. J. 2010, 16, 5310.
(5) For the synthetic details as well as the structural characterization,
see the Supporting Information.
(6) (a) Newcomb, M.; Tanaka, N.; Bouvier, A.; Tronche, C.; Horner,
J. H.; Musa, O. M.; Martinez, F. N. J. Am. Chem. Soc. 1996, 118, 8505.
(b) Horner, J. H.; Tanaka, N.; Newcomb, M. J. Am. Chem. Soc. 1998,
120, 10379.
r
10.1021/ol201112a
Published on Web 06/06/2011
2011 American Chemical Society

of both cyclopropane rings,6 upon an electron transfer
reaction with C60 (vide infra), as previously observed in
related monocyclopropane analogues.3 Accordingly, it
should be expected that rearranged biscyclopropane deriva-
tives 9 and 10 could spontaneously cyclize with C60 to form
n-membered fused ring systems (for alkene 9, n = 5, 7, 8, 10;
for alkene 10, n = 5, 7ꢀ10, 12).
It should be noted that the isolation of isomers 9aꢀd was
not a trivial endeavor. It was only achieved after laborious
chromatographic separation, including a two-step semi-
preparative HPLC process (for details see the Supporting
Information (SI)). To demonstrate the difficulty of HPLC
separations for 9a and 9b stereoisomers (1:1, major
products), Figure S15 indicates elution differences of only
129 and 124 min, respectively, and a clear lack of baseline
resolution. These stereoisomers were effectively separated
and purified after successive recycling of overlapping sub-
fractions. The mixture of 9c and 9d isomers was found to
be inseparable under several conditions which, however,
did not prevent their structural characterization.
Scheme 1. Preparation of Compounds 9 and E,Z-10
The structure of all new fullerene adducts has been
unambiguously established by the combined use of 1D
1
and 2D NMR techniques (1H, 13C, 1Hꢀ H COSY,
13
1
13
1
1Hꢀ C HMQC, Hꢀ C HMBC, H homonuclear de-
1
1
coupling and Hꢀ H NOE difference), UV/vis spectro-
scopy, and high resolution mass spectrometry (see the SI).
In particular, the NMR spectra of the isolated products all
exhibit similar 1H/13C NMR patterns, showing them to be
diastereomers of cis-1 tricyclic 5ꢀ4ꢀ5-fused fullerenes
9aꢀd, thus demonstrating the totally regioselective nature
of the 2-fold cycloaddition of 9 across the same hexagonal
ring of C60 (Scheme 2). The 13C NMR spectra of C1
symmetric compounds 9aꢀd each display 60 resonances
for the fullerene carbon atoms: 56 sp2 resonances in the
region of 133.1ꢀ156.1 ppm and four single intensity
characteristic resonances in the region 67.4ꢀ71.5 ppm
which, based on HMQC experiments, are assigned to
sp3-hybridized fullerene carbons. The absence of the char-
acteristic cyclopropyl proton absorption in the upfield 1H
NMR region (∼0.5ꢀ2.3 ppm) indicates cyclopropane
ring-opened structures for compounds 9aꢀd. Moreover,
the 1H NMR spectrum of these adducts shows, apart from
the existence of two methyl group resonances at 1.82ꢀ2.00
ppm, the presence of the characteristic vinyl proton of
9aꢀd, which appears as a doublet centered at 5.64ꢀ5.90
ppm with a coupling constant of 3JHH = 9.5ꢀ10 Hz. The
HꢀH coupling pattern in isolated products was deduced
Initially, the reaction of C60 with a 30-fold excess of 9 in
deoxygenated toluene was investigated. No products were
observed at solvent reflux in the absence of light for 12 h,
whereas this reaction took place readily upon irradiation
using a xenon lamp (Variac Eimac Cermax 300 W, λ > 280
nm) at 5ꢀ10 °C. Reversed-phase HPLC analysis of the
reaction mixture showed two major, partially overlapping
peaks after 5 h of irradiation. These peaks corresponded to
a complex mixture of C60 cycloadducts. Contrary to our
initial expectations, the only compounds obtained from
this mixture in 60% yield (80% based on recovered C60)
were assigned as the unanticipated cis-1 tricyclic-fused
fullerene derivatives 9aꢀd (Scheme 2). To the best of our
knowledge, this is the first example of a fused 5ꢀ4ꢀ5
tricyclic ring system on the same fullerene hexagonal ring.
The end resultof thisreaction may beregardedasa tandem
(3 þ 2) cycloaddition of two cyclopropyl rings into adja-
cent double bonds of C60.
1
1
13
by H homonuclear decoupling, Hꢀ C HMBC, and
1
1Hꢀ H COSY experiments (see the SI) giving results
consistent with the assignment of structures 9aꢀd. Differ-
ence nuclear Overhauser effect (DNOE) experiments pro-
vided all spatial proximity information, including the
cis/trans stereochemistry of the 1,3-cyclopentane substitu-
ents, and confirmed the formation of these cyclic adducts
as shown in Figure 1 (also see Figure S40, SI). The energy-
minimized molecular structures of 9aꢀd obtained from
molecular mechanics calculations (Figure 1) correlate
perfectly with the information obtained from the spectro-
scopic analysis. More importantly, the coupling constant
values between the neighboring cyclopentane protons
Scheme 2. Reaction of 9 with C60 in Toluene
support their anti or syn relative configuration (3JHH(syn)
=
3
6ꢀ9.5 Hz and JHH(anti) = 9.5ꢀ13.5 Hz) as depicted in
Figure 1.
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Org. Lett., Vol. 13, No. 13, 2011
3365

[M þ H]þ, consistent with the molecular weight of 9aꢀd.
The above spectral studies all support the C1 symmetric
structures of 9aꢀd with cis-1 regiochemistry, as depicted
in Figure 1.
Figure 2. UV/vis spectra of compounds 9aꢀd.
Figure 1. MM2-optimized structures of 9aꢀ9d (the cyclopentane
hydrogens, red; the carbon framework of the addend, yellow; the
corresponding hexagonal fullerene framework, green).
Although much faster (10 °C, 30 min), the reaction of C60
with 10 afforded again in high yield (80%) an even more
complex mixture of several stereoisomers apparently due to
the presence of an extra double bond that increased the
number of possible stereoisomers. This complex mixture was
difficult to separate and could not be fully characterized.
Importantly, however, the spectral analysis of this crude
mixture indicated again the formation of cis-1 stereoisomers,
thus validating the versatility of the present method.
Further evidence is provided by UVꢀvis spectroscopy,
which has proven to be a powerful tool in determining
the addition pattern of C60 bisadducts; the electronic absorp-
tion spectra of [60]fullerene bisadducts are typically sensitive
toward the addition pattern rather than the type of addends.8ꢀ10
Herein, the UV/vis absorption spectra of compounds 9aꢀd
exhibit the typical features of the hitherto known cis-1
bisadducts, with a characteristic absorption at 433 nm,
together with shoulders at 334 nm (Figure 2).9ꢀ17 Finally,
the high-resolution FAB mass spectra of 9aꢀd exhibit
pseudomolecular ion peaks at m/z 933.1630ꢀ933.1652
The precise mechanism involved in this reaction is still
unclear, but the unique structure of the observed products
9aꢀd provides strong evidence for its rationalization. A
plausible mechanism for the addition of 9 to C60 is depicted
in Scheme 3. Specifically, the mechanism should be in-
itiated by photoinduced electron transfer (PET) from the
double bond of 9 to 3C60*, thus forming the corresponding
geminate radical ion pair. The incipient radical cation 9I
undergoes a facile ring opening of the two cyclopropane rings
to form 9III before combining with its geminal radical anion
3C60•ꢀ. In each case, a regiospecific cleavage of the more
substituted cyclopropane bond occurs, by virtue of the
stability of a secondary over a primary carbon radical. At
this point forward, two reaction pathways may be considered
for the coupling of the radical ion pair. On one hand
(pathway A), the coupling of distonic radical cation 9III with
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•ꢀ
C60 produces 1,4-cycloadduct 9V which, in turn, sponta-
ꢁ
A.; Sola, M.; Martın, N. J. Org. Chem. 2009, 74, 6253. (b) Martın, N.;
€
ꢀ
Altable, M.; Filippone, S.; Martın-Domenech, A.; Guell, M.; Sola, M.
neously undergoes an intramolecular [2 þ 2] photocycload-
dition reaction to produce the final adducts 9aꢀd. Thefacility
of this latter process may be ascribed, at least in part, to the
release of the strain induced by the energetically unfavorable
C2dC3 double bond at a [5,6] ring junction of C60. On the
other hand (pathway B), radical coupling of 9III with
C60•ꢀ followed by an intramolecular nucleophilic addi-
tion to the proximal double bond generates in situ the
1,3-dipolar intermediate 9VII which, ultimately, cyclizes
to adducts 9aꢀd via an intramolecular 1,3-dipolar addi-
tion to the adjacent [6,6]-double bond of C60.
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3366
Org. Lett., Vol. 13, No. 13, 2011

this is the first example of such an elegant cycloaddi-
tion reaction that provides a highly efficient route for the
direct and completely regioselective cis-1 functionalization
of C60.20
Scheme 3. Proposed Mechanism for the Cycloaddition of 9 and
C60, under PET Conditions
In summary, we have disclosed a tandem (3 þ 2)
cycloaddition of vinyl biscyclopropane derivatives with
C60. This novel reaction affords, in a single synthetic step,
smoothly, and in good yield, a novel class of fullerene cis-1
bisadducts containing the hitherto elusive 5ꢀ4ꢀ5 tricyclic
fused ring system. The reaction is totally regioselectivethus
demonstrating its potential for sterically demanding full-
erene functionalizations such as the construction of highly
congested 1,2,3,4-tetrahydro[60]fullerene derivatives.
Further exploration of the characteristics and scope of this
novel reaction is currently in progress.
Acknowledgment. This work was supported by the
Greek State Scholarships Foundation (I.K.Y.) through a
postdoctoral research scholarship awarded to M.D.T. and
M.N.A. The Foundation for Education and European
Culture is also acknowledged for providing a one year
fellowship to M.N.A. We are also grateful to Professors K.
Komatsu and Y. Murata at Kyoto University for perform-
ing the HRMS analyses.
At this point it is worth noting that 1,2,3,4-tetrahydro-
[60]fullerenes display interesting photophysical properties.18
They have also attracted considerable research interest due
to their utility as ideal precursors of open-cage fullerenes
through a stepwise approach of saturating all three double
bonds of a six-membered ring on C60.11,19 More importantly,
Supporting Information Available. Detailed experi-
mental procedures, spectral data, and copies of 1D/2D
NMR, HRMS, and UVꢀvis spectra. This material is
available free of charge via the Internet at http://pubs.
acs.org.
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